This invention relates generally to an isotopic generator system as a source of bismuth-212 and lead-212 radionuclides. More particularly, the invention relates to an isotopic generator system which uses thorium-228 starting material in a radiologically contained portion of the system for producing radionuclides of bismuth-212 and lead-212 from an ion exchange column in an accessible generator portion of the system.
The practice of medical radiotherapy has previously involved the use of short lived .alpha.-emitting isotopes, such as .sup.211 At, and a .beta. emitter, such as .sup.131 I (see, for example, Zucchini et al., "Isotopic Generator for .sup.212 Pb and .sup.212 Bi", International J. Nucl. Med. Biol. 9, 83 (1982); and Gansow et al., "Generator Produced Bi-212", American Chemical Society Symposium Series No. 214, January, 1984, which are incorporated by reference herein). In the case of cancer therapy, isotopes of lead-212 and bismuth-212 are combined in a chelated form with monoclonal antibodies which have a high specificity for cancer cells (see Zucchini and Gansow). However, in the case of .sup.211 At and .sup.131 I because both are halogens, there is a covalent reaction with tyrosine residues present in the antibody material, and there can be a consequent diminishment in activity and in the specificity for cancer cells. Furthermore, .sup.131 I delivers only low linear energy transfer .beta..sup.- radiation which is not as effective as high linear energy transfer radiation, such as .alpha.-particles. Further, .sup.131 I emits .gamma. rays which have the undesired effect of nonlocalized destruction of cells somewhat removed from the origin of the .gamma. emIssIon. The .sup.211 At aIso must be produced by .alpha.-particle irradiation of bismuth in a cyclotron which limits the quantity of material produceable at a reasonable price. More recently, a chelated form of lead-212 has been used for immune suppression purposes, (see, M. K. Rosenow, "Properties of Liposomes Containing Pb-212", Intl. J. Nucl. Med. Biol. 10. 189-197, 1983). Further, a chelated form of bismuth-212 has been combined with monoclonal antibodies to provide a more stable radiotherapy agent with a high specificity for cancer cells. (see, p. 83 of Zucchini et al., cited hereinbefore). The bismuth-212 radionuclide is generated from decay of thorium-228 into radium-224 and radon-220 gas. The radon-220 gas is dissolved in water and separated from the thorium-228. Radon-220 has a half life of about one minute, and decay of the radon-220 leads to formation of lead-212 and consequent decay to bismuth-212. The short time for the decay of the radon-220 to form the desired lead-212 and its decay product, bismuth-212, makes it necessary to maintain the entire column as one unit. The long half life of 1.9 years for thorium-228 and the high level of radioactivity associated with the thorium-228, requires the use of a containment unit, such as a shielded facility or shielded glove box, for safe handling of the generator system. Furthermore, the ion exchange column used to retain the thorium-228 and the radium-224 undergoes substantial radiation damage degradation which requires periodic disassembly and reconstruction of the generator system. This particular prior art thorium-228 based generator system also necessitates periodic repurification of the thorium-228 source.
It is therefore an object of the invention to provide an improved method and apparatus for producing bismuth-212 and lead-212 radionuclides.
It is a further object of the invention to provide an improved generator system for producing bismuth-212 and lead-212 radionuclides from thorium-228 starting material.
It is another object of the invention to provide an improved radionuclide generator system having a radiologically contained portion with a plurality of valves for collection of radium-224 to enable formation and withdrawal of bismuth-212 and lead-212 from an ion exchange column in an accessible portion of the system which can be removed and utilized apart from the contained portion of the system.
It is an additional object of the invention to provide an improved radionuclide generator system which uses thorium-228 starting material disposed in a radiologically contained portion for producing radium-224 in an ion exchange column in an accessible generator portion which is removable from the contained portion and wherein a cation exchange media is used to retain the radium-224 to enable selective removal of bismuth-212 and lead-212.